Indices of hemodynamic and respiratory functions in premature infants at risk for the development of cerebral white matter injury.

OBJECTIVE: To examine potential differences in clinical risk factors, including indices of hemodynamic and respiratory functions, of premature infants developing periventricular hemorrhagic infarction (PHI) or periventricular leukomalacia (PVL). STUDY DESIGN: Indices of hemodynamic stability and respiratory function were measured prospectively during the first week of life in a cohort of 100 premature infants with respiratory distress. Maternal history was retrospectively reviewed. These data were correlated with cranial ultrasonography using one-way ANOVA, Bonferroni multiple comparisons, and Wilcoxon rank sum tests. Longitudinal analysis was performed using Generalized Estimating Equations. RESULTS: Fifty-two infants with normal cranial ultrasound studies were compared to 12 with PHI and 9 with PVL. Infants developing PHI had significantly lower birth weights, lower Apgar scores, were more often male and multiple gestations, and required more vasopressor support than infants with normal ultrasound studies. Infants with PHI had significantly worse indices of respiratory function than either normal infants or those with PVL. PVL was significantly associated with maternal chorioamnionitis, whereas PHI was not. CONCLUSION: These data suggest that there are important differences in the pathogenesis of PHI and PVL. A clear understanding of these differences is required before future preventive strategies can be formulated.     

Placental morphology in cytomegalovirus infection

Three groups of placentae from 27 cases of cytomegalovirus infection were examined morphologically and by specific immunofluorescence. Placentae in Group 1 (four cases) had a mean gestational age of 24.5 +/- 2.5 weeks; those in Group 2 (11 cases) had a mean gestational age of 36.4 +/- 2.7 weeks; those in Group 3 (12 cases) had a mean gestational age of 40 +/- 1.8 weeks. A tendency towards increased placental weight was observed. In 23 cases, a haematogenous placentitis was suspected on gross examination. Some specific features were detected on light microscopy. In Group 1 the lesions were represented by pronounced dysmaturity of villous structures, diffuse reparative villitis and intervillitis allied to an abundance of cytomegalic cells and areas of necrosis and calcification. In Group 2 a chronic active process was indicated by the presence of vascular involvement, proliferative-necrotic and reparative villitis and fresh villous necrosis; cytomegalic cells were scarce. In Group 3 placentae there was a predominance of villous plate lesions similar to those found in the septicaemic phase of maternal infections; necrotizing, proliferative and, rarely, reparative villitis was present; cytomegalic cells were rare. We may conclude that placental morphology needs to be substantiated by special laboratory techniques for the detection of cytomegalovirus infection.     

Three-dimensional sonographic features of placental abnormalities

OBJECTIVE: To describe three-dimensional (3D) sonographic features of placental abnormalities in utero. METHODS: A total of 6 cases with placental abnormalities (1 chorioangioma, 1 subchorionic hematoma, 2 placental cysts, and 2 subplacental fibromas) from 22 to 34 weeks of gestation were studied with transabdominal 3D sonography. RESULTS: Placental abnormalities could be easily imaged with both two-dimensional (2D) and 3D sonography; however, visualization of the continuity and curvature of structures was more easily accomplished with 3D sonography. In the case with chorioangioma, the thick and rough surface of the tumor was clearly depicted. With the use of color Doppler ultrasound, only a case of chorioangioma was shown to have abundant blood flow within the tumor. In cases with placental cyst and subchorionic hematoma, the wall of the cyst becomes a transparent-like structure, so internal textures can be clearly identified. In the case with subplacental fibroma, the location in relation to the placenta was clearly recognized. CONCLUSION: These results suggest that 3D sonography has the potential to be a supplement to 2D sonography and color Doppler ultrasound in identifying placental masses and provides a novel means of visualizing placental abnormalities in utero.     

Placental pathology and cerebral palsy

Recent classification systems of cerebral palsy call for an assessment of the timing and etiology of brain injury. The placenta is an underused resource for addressing these important questions. An expert assessment of the placental pathology can provide temporally and mechanistically specific data not available from any other source. Key concepts for an understanding of the role of placental pathology are the "sentinel lesion," the high prevalence of thromboinflammatory lesions affecting large fetal placental vessels, the significance of underlying placental reserve, and the realization that placental findings can serve as markers for processes occurring in the mother or fetus.     

子痫前期头颅磁共振异常高危因素分析

目的:探讨子痫前期头颅磁共振异常的高危因素.方法:回顾分析2017年1月至2019年12月在南京大学医学院附属鼓楼医院妇产科分娩的子痫前期及慢性高血压并发子痫前期并接受头颅磁共振检查者,根据影像学检查结果,分为磁共振异常组和正常组.比较两组孕妇的一般临床资料、入院后血压评估、实验室检查结果,通过二元logis-tic回...     

Neonatal nucleated red blood cells and the prediction of cerebral white matter injury in preterm infants

OBJECTIVE: To estimate whether neonates with cerebral white matter injury have significant elevations in nucleated red blood cell counts and to estimate their predictive ability in identifying injury. METHODS: This case-control study identified 176 infants born at 23-34 weeks of gestation between November 1994 and October 2004 at a single university hospital and with cerebral white matter injury characterized by periventricular leukomalacia (PVL) or ventriculomegaly due to white matter atrophy. A control was matched to each case using the subsequent delivery within 7 days of that gestational age without brain injury. RESULTS: The gestational age at birth was 27 weeks for both groups, but the cases had a significantly lower birth weight (mean +/- standard deviation: 958 +/- 306 g compared with 1,038 +/- 381 g, P = .001). There was no difference in cesarean delivery (48% cases compared with 44% controls, P = .59). The cases had a significant increase in nucleated red blood cells per 100 white blood cells (WBC) (median, 5th percentile and 95th percentile: 22, 3 and 374 cases compared with 14, 1 and 312 controls; P = .02). Markers of chronic hypoxia, such as intrauterine growth restriction and oligohydramnios, and markers of acute hypoxia, such as an umbilical arterial pH less than 7.0 or base excess less than -12 mM, were both associated with significantly elevated neonatal nucleated red blood cell counts. A neonatal nucleated red blood cell count of 18 per 100 WBCs had a sensitivity of 56.9%, specificity of 57.9%, positive predictive value of 57.9%, and negative predictive value of 56.9% in predicting the development of cerebral white matter injury in this matched case-control sample. CONCLUSION: Preterm neonates with cerebral white matter injury have significant increases in nucleated red blood cell counts. Both acute and chronic hypoxia-ischemia can increase these counts, which limits their usefulness in timing injury. The predictive value of nucleated red blood cell counts at birth in identifying injury is poor. LEVEL OF EVIDENCE: II-2.     

Proinflammatory cytokine-receptor interaction model improves the predictability of cerebral white matter injury in preterm infants

Proinflammatory cytokines have been variably linked to development of cerebral white matter injury (WMI) in preterm infants. Because soluble receptors tightly control cytokine bioactivity, we modeled cytokine-receptor interaction as a predictor of WMI. Plasma from 100 preterm infants was assayed for cytokines (tumor necrosis factor alpha, interleukin (IL-1beta, IL-6) and their soluble receptors (sTNF-RI), sTNF-RII, sIL-1RA, and sIL-6R). Cranial ultrasound (US) results were correlated with cytokine and receptor concentrations individually and with cytokine-receptor interaction models (PROC LOGISTIC; SAS Software). Receiver operating characteristic curves were constructed to determine the predictability of WMI. Fifty-two infants with normal US exams were compared with 21 infants with evidence of WMI. There was no association between individual cytokine or receptor concentrations and the development of WMI. However, modeling cytokines with their soluble receptors significantly improved the predictability of WMI. We concluded that consideration of cytokine-receptor interaction may be more important than individual cytokine concentrations alone in determining the role of inflammation in the pathogenesis of WMI in preterm infants.     

Ultrasonographic differential diagnosis and neurodevelopmental outcome of cerebral white matter lesions in premature infants.

OBJECTIVE: To determine the clinical usefulness of recently published ultrasonographic criteria for the differential diagnosis of periventricular hemorrhagic venous infarction (PHVI) versus periventricular leukomalacia (PVL), and its relevance to neurodevelopmental outcome. STUDY DESIGN: From 1992 to 1995, we evaluated 998 very low birth weight infants of which 111 developed cerebral white matter lesions on cranial ultrasonogram examination. An attempt was made to differentiate the lesions into either PHVI or PVL using specific ultrasonographic criteria (Volpe JJ. Brain inury in the premature infant: is it preventable? Pediatr Res 1990; 6:S28-33). Seventy-six patients who survived to discharge constituted the study group. Survivors were followed prospectively with neurologic examinations, visual and auditory screening, and developmental testing. RESULTS: PHVI was diagnosed in 23 patients (30%), PVL in 36 (47%), characteristics of both PHVI and PVL (mixed lesions) in 8 (11%), and persistent periventricular echodensity without cystic change in 9 (12%). Two-year follow-up data were obtained on 57 of 76 (75%) patients. Neurodevelopmental deficits were common in all groups; however, infants with localized PHVI had a mean developmental quotient in the normal range. CONCLUSION: The majority of white matter lesions (77%) can be differentiated as either PHVI or PVL by ultrasonographic criteria, with coexisting features in only 11% of patients. In addition to these lesions, persistent periventricular echodensity was also associated with a high risk of subsequent neurodevelopmental deficit. However, normal development was seen in a subgroup of patients with localized periventricular hemorrhagic venous infarction.     

Transvaginal sonographic detection of embryonic-fetal abnormalities in early pregnancy

OBJECTIVE: To estimate the detection rate of abnormalities by transvaginal ultrasound in early pregnancy. METHODS: We prospectively analyzed records of 3592 sequential pregnant women at 10-16 weeks' (singleton) gestation (mean 13 weeks and 2 days). After exclusion of 114 women, there were 3478 women in the study. Each woman underwent a transvaginal sonographic survey for fetal anomalies as well as biometric measurements. Fetuses diagnosed with malformations were followed to delivery, and those without underwent transabdominal sonography at 18-24 weeks' gestation.Results: The anomaly detection rate by transvaginal ultrasound was 51.6% (33 of 64; 95% confidence interval [CI] 38.7, 64.2) in early pregnancy, and the detection rate by transvaginal ultrasound combined with second-trimester transabdominal ultrasound was 84.4% (54 of 64; 95% CI 73.1, 92.2). Cystic hygroma and fetal hydrops were the anomalies detected most frequently by transvaginal ultrasound. Low detection rates for abnormalities of the face and of the cardiac, skeletal, and urinary systems were found even when both methods were used. CONCLUSION: Transvaginal sonography appears to be an effective way to identify many congenital fetal anomalies in early pregnancy. There is a good probability of diagnosing cystic hygroma and fetal hydrops, although other abnormalities, particularly heart defects, are associated with lower detection rates.     

Cerebral white matter lesions and silent cerebral infarcts in postmenopausal women with polycystic ovary syndrome

Objectives: The association between polycystic ovary syndrome (PCOS) and cardiovascular disease remains unclear. Our objective was to examine the relation of PCOS with cerebrovascular disease measured by brain magnetic resonance imaging (MRI) as white matter lesions (WMLs) and silent cerebral infarcts (SCIs).

Methods: Seventy postmenopausal women with PCOS and 140 controls participated in the case–control, cross-sectional study. Clinical, anthropometric, hormonal and metabolic parameters were measured. WMLs and SCIs were evaluated by brain MRI.

Results: Compared with controls, postmenopausal women with PCOS had higher mean body mass index, larger waist hip ratio, higher level of low-density lipoprotein cholesterol, free androgen index and lower sex hormone-binding globulin level. The PCOS group had a significantly higher prevalence of WMLs (40% versus 22%, p?=?0.009), and SCIs (17% versus 7%, p?=?0.032) compared to the control group.

Conclusions: Postmenopausal women with PCOS are associated with WMLs and SCIs.     

早产儿脑白质损伤早期磁共振成像改变及其高危因素分析

摘要：目的　以磁共振成像（MRI）提供的影像学资料为依据,评价早产儿脑白质损伤的早期MRI变化及其临床意义,并探讨其高危因素。方法　选取2007年9月至2009年9月中国医科大学附属盛京医院儿科收治的262例早产儿,全部在7 d内完成磁共振检查,根据MRI诊断早产儿脑白质损伤,分为病例组134例,对照组128例。并对病例组29例患儿进行二次复查。结果　（1）早产儿脑白质损伤早期,局灶性病变表现弥散加权成像（DWI）高信号,T1加权（T1WI）信号正常或稍高信号,伴有或不伴有T2加权（T2WI）低信号;弥漫性脑白质损伤仅能看到DWI弥漫性高信号,常规MRI无信号改变。复查结果,局灶性病变有两种情况：一是病灶消失,二是DWI高信号消失或稍高信号,T1WI高信号,伴或不伴有T2WI低信号;弥漫性病变,发生脑室周围白质软化,表现为T2WI高信号或高低混杂信号, DWI异常信号消失或高低混杂信号,T1WI高低混杂信号。（2）病例组与对照组在胎龄,出生体重差异无统计学意义。单因素分析：母孕期感染、双胎、代谢性酸中毒、低钙、低氧、机械通气和感染与早产儿早期脑白质损伤有统计学意义。Logistic模型多因素分析,母孕期感染、低氧和胎儿宫内窘迫是早产儿早期脑白质损伤的危险因素。结论　（1）DWI能发现早期脑白质损伤病变。（2）早产儿脑白质损伤是多种因素相互作用的结果：母孕期感染、胎儿宫内窘迫及出生后低氧与早产儿早期脑白质损伤有密切关系。（3）早产儿脑白质损伤早期临床表现缺乏特异性,建议常规行头MRI检查,且脑白质信号异常均需要动态随访观察。     

Placental morphology in pregnancies associated with pregravid obesity

Objective: Pre-gravid obesity is associated with increased morbidity and mortality for both mother and offspring. We aimed to investigate the changes in placental structure and to characterize the placental inflammatory status in obese women.

Methods: Placentas from 10 women with pregravid body mass index?≥?30?kg/m² were analyzed histopathologically and compared with those from 10 normal weight women. The effect of pregravid obesity on placental structure was investigated by examining placental maturity, angiogenesis, inflammatory response, and vascular abnormalities. Hematoxylin and eosin stain, immunohistochemical analysis, and morphometric analysis were performed.

Results: Immaturity of the villous tree was demonstrated more often in the pregravid obesity group (p?=?0.005). The villous tree was mainly represented by villi of larger diameter (p?=?0.001) and lower number (p?=?0.023) compared with controls. By contrast, the number of capillaries per villus was increased in the obese group (p?=?0.001), while the global number of capillaries per surface unit did not differ in the studied groups (p?=?1). There was no difference between the pre-gravid obese group and controls in inflammatory status and vascular pathology.

Conclusions: Pregravid obesity is associated with focal immaturity of the villous tree and angiogenetic abnormalities of the placenta.     

Nuchal translucency and other first-trimester sonographic markers of chromosomal abnormalities

There is extensive evidence that effective screening for major chromosomal abnormalities can be provided in the first trimester of pregnancy. Prospective studies in a total of 200,868 pregnancies, including 871 fetuses with trisomy 21, have demonstrated that increased nuchal translucency can identify 76.8% of fetuses with trisomy 21, which represents a false-positive rate of 4.2%. When fetal nuchal translucency was combined with maternal serum free-beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A in prospective studies in a total of 44,613 pregnancies, including 215 fetuses with trisomy 21, the detection rate was 87.0% for a false-positive rate of 5.0%. Studies from specialist centers with 15,822 pregnancies, which included 397 fetuses with trisomy 21, have demonstrated that the absence of the nasal bone can identify 69.0% of trisomy 21 fetuses, which represents a false-positive rate of 1.4%. It has been estimated that first-trimester screening by a combination of sonography and maternal serum testing can identify 97% of trisomy 21 fetuses, which represents a false-positive rate of 5%, or that the detection rate can be 91%, which represents a false-positive rate of 0.5%. In addition to increased nuchal translucency, important sonographic markers for chromosomal abnormalities, include fetal growth restriction, tachycardia, abnormal flow in the ductus venosus, megacystis, exomphalos and single umbilical artery. Most pregnant women prefer screening in the first, rather than in the second, trimester. As with all aspects of good clinical practice, those care givers who perform first-trimester screening should be trained appropriately, and their results should be subjected to external quality assurance.     

Gestational age at glucocorticoids administration after premature rupture of membranes and cerebral white matter damage

Objective.?We investigated whether gestational age at glucocorticoids administration in very preterm premature rupture of membranes (PROM) affects the occurrence of neonatal cerebral white matter damage (WMD).

Methods.?In a cohort of singleton neonates born at 24.0–33.6 weeks after PROM who underwent at least one full course of glucocorticoids (n?=?130), we compared the gestational age at first and last course of glucocorticoids between those who developed WMD (n?=?8) and those who did not (n?=?122) after adjusting for gestational age at PROM using logistic regression with P?<?0.05 considered significant.

Results.?Gestational age at first course of glucocorticoids (P?=?0.2), at last course of glucocorticoids (P?=?0.2) and at delivery (P?=?0.2), were not significantly different between those who developed WMD and those who did not. Although latency between PROM and first course of glucocorticoids was protective against WMD (P?=?0.02), the significance was lost after controlling for gestational age at PROM, which was significantly lower in cases that developed WMD (P?<?0.01).

Conclusions.?In very preterm PROM, the beneficial effect of glucocorticoids on occurrence of WMD is not related to gestational age at steroid administration.     

Trisomies and other chromosome abnormalities detected after positive sonographic findings

OBJECTIVE: To evaluate the rate of trisomies and other chromosome abnormalities after positive ultrasound findings in thefirst and second trimester of pregnancy. STUDY DESIGN: The study investigated chromosome abnormalities detected in cases with prior abnormal ultrasoundfindings. During a 10-year period there were 1907 invasive interventions carried out with the purpose of chromosome analysis. The intervention was genetic amniocentesis in 1619 cases and chorionic villus sampling in 288. RESULTS: Karyotyping revealed 103 cases (5.4%) of chromosome abnormalities. Abnormalities with subcutaneous edema were examined: abnormal karyotype was found in 20% of cases with nonimmune hydrops, 48.1% of cases with cystic hygroma and 53.8% of cases with nonimmune hydrops and cystic hygroma together, 8.3% of cases with nuchal edema in the first trimester and 5.5% in the second trimester. The incidence of chromosome abnormalities in cases of cerebral anomalies was 6.3% of cases with ventricular dilatation, 3.6% of cases with choroid plexus cysts and 15.9% of cases with other cranial anomalies. Regarding abnormalities of the heart, isolated echogenic intracardiac focus and ventricular septal defects were not associated with chromosome abnormality, but, in conjunction with other positive ultrasound findings, the incidence of chromosome abnormalities was 7.9% and 26.7%, respectively. Other anomalies of the heart and large blood vessels showed an abnormal karyotype incidence of 18.2%. In cases of unilateral pyelectasis unassociated with other anomalies, the incidence of chromosome abnormalities was 1%. In cases of bilateral pyelectasis or pyelectasis associated with other anomalies, the incidence was 3%. In terms of anomalies of the abdominal wall and abdomen, the incidence of association with chromosome abnormalities was 9.5% in cases of omphalocele, 11.8% in cases of duodenal atresia and 5.7% in cases of echogenic bowel. In cases of short femur and humerus the rate of abnormal karyotypes was 16%. CONCLUSION: Ultrasound plays an important role in prenatal diagnosis. In cases of positive ultrasound findings, karyotyping is reasonable.     

First trimester sonographic detection of chromosomal abnormalities in an unselected population

Objective To investigate the role of first trimester sonography in detecting chromosomal abnormalities in an unselected obstetric population.
Methods 2281 women (mean maternal age 30 years [range 16-47]; mean gestational age 12⁺³ weeks [range 11-14]) underwent transabdominal scanning to assess fetal structure and, if anatomical survey was considered to be incomplete (31% of cases), transvaginal sonography was also performed. Measurement of nuchal translucency was included and karyotyping performed as considered appropriate.
Results There were 16 chromosomal abnormalities; 13 (81%) were diagnosed at 11-14 weeks either because of a nuchal translucency greater than or equal to the 99th centile for gestational age (7/16; 44% [95% CI 25-63]) or due to the presence of structural abnormalities (6/16; 38% [95%CI 14.2–61.81). Seventy-five percent of cases of trisomy 21 were also diagnosed either because of having a nuchal translucency greater than or equal to the 99th centile (5/8; 63%) or due to the presence of a structural abnormality (1/8; 13%).
Conclusions A significant proportion of fetal chromosomal abnormalities can be detected by first trimester sonographic screening to assess fetal structural appearance. The sensitivity of detection can be improved by combining measurement of nuchal translucency with detailed examination of fetal anatomy.     

Placental abnormalities associated with isolated single umbilical artery in small-for-gestational-age births

BackgroundPrevious studies have shown that pregnancies complicated by placentas with an isolated single umbilical artery (iSUA) are at increased risk for small-for-gestational-age (SGA) births. The etiology of SGA in this population, however, remains unknown.ObjectiveThe primary objective of this study was to evaluate whether placental abnormalities in pregnancies with SGA births differ according to the presence of iSUA.Study designThis was an observational study of all women with pathologic examination of the placenta after delivering a non-anomalous, singleton SGA neonate between January 2009 and August 2015. SGA was defined as birthweight less than 10th percentile for gestational age. Women were categorized according to whether they had an iSUA or a three-vessel cord. The following placental pathologies were compared between the groups using bivariable and multivariable analyses: SGA placenta, maternal vascular malperfusion, high grade fetal vascular malperfusion, and chronic villitis.Results1833 women were included in the analysis: 34 with iSUA and 1799 with three-vessel cord. More than 85% of women in both groups had at least one placental abnormality. After adjusting for nulliparity and neonatal gender, the presence of iSUA was associated with increased odds of high grade fetal vascular malperfusion (adjusted odds ratio 2.8, 95% confidence interval 1.1–7.5) and decreased odds of maternal vascular malperfusion (adjusted odds ratio 0.2, 95% confidence interval 0.1–0.9). There was no significant association with other pathologic findings.ConclusionPathologic placental findings associated with SGA birth differed based on umbilical cord composition. The presence of iSUA in an SGA birth was associated with a higher odds of high grade fetal vascular malperfusion abnormalities and lower odds of maternal vascular malperfusion abnormalities, compared to SGA birth with a 3VC.